Different dermal cell types have been reported to differ in their sensitivity to nano-sized TiO₂ . Kiss et al. exposed human keratinocytes (HaCaT), human dermal fibroblast cells, sebaceous gland cells (SZ95) and primary human melanocytes to 9 nm-sized TiO₂ particles at concentrations from 0.15 to 15 μg/cm² for up to 4 days. The particles were detected in the cytoplasm and perinuclear region in fibroblasts and melanocytes, but not in kerati-nocytes or sebaceous cells. The uptake was associated with an increase in the intracellular Ca²⁺ concentration. A dose- and time-dependent decrease in cell proliferation was evident in all cell types, whereas in fibroblasts an increase in cell death via apoptosis has also been observed. Anatase TiO₂ in 20–100 nm-sized form has been shown to be cytotoxic in mouse L929 fibroblasts. The decrease in cell viability was associated with an increase in the production of ROS and the depletion of glutathione. The particles were internalized and detected within lysosomes. In human keratinocytes exposed for 24 h to non-illuminated, 7 nm-sized anatase TiO_2, a cluster analysis of the gene expression revealed that genes involved in the “inflammatory response” and “cell adhesion”, but not those involved in “oxidative stress” and “apoptosis”, were up-regulated. The results suggest that non-illuminated TiO₂ particles have no significant impact on ROS-associated oxidative damage, but affect the cell-matrix adhesion in keratinocytes in extracellular matrix remodelling. In human keratinocytes, Kocbek et al. investigated the adverse effects of 25 nm-sized anatase TiO₂ (5 and 10 μg/ml) after 3 months of exposure and found no changes in the cell growth and morphology, mitochondrial function and cell cycle distribution. The only change was a larger number of nanotubular intracellular connections in TiO₂-exposed cells compared to non-exposed cells. Although the authors proposed that this change may indicate a cellular transformation, the significance of this finding is not clear. On the other hand, Dunford et al. studied the genotoxicity of UV-irradiated TiO₂ extracted from sunscreen lotions, and reported severe damage to plasmid and nuclear DNA in human fibroblasts. Manitol (antioxidant) prevented DNA damage, implying that the genotoxicity was mediated by ROS.

All in all, Titanium Dioxide is a famous sunscreen agent and for good reason, it gives broad spectrum UV protection (best at UVB and UVA II), it's highly stable, and it has a good safety profile. It's definitely one of the best UV-filter agents we have today, especially in the US where new-generation Tinosorb filters are not (yet) approved. 

Micronized titanium dioxide doesn’t penetrate skin so there’s no need to be concerned about it getting into your body. Even when titanium dioxide nanoparticles are used, the molecular size of the substance used to coat the nanoparticles is large enough to prevent them from penetrating beyond the uppermost layers of skin. This means you’re getting the sun protection titanium dioxide provides with no risk of it causing harm to skin or your body. The coating process improves application, enhances sun protection, and prevents the titanium dioxide from interacting with other ingredients in the presence of sunlight, thus enhancing its stability. It not only makes this ingredient much more pleasant to use for sunscreen, but also improves efficacy and eliminates safety concerns. Common examples of ingredients used to coat titanium dioxide are alumina, dimethicone, silica, and trimethoxy capryl silane.

But in the U.S., titanium dioxide is found all over the grocery shelves. Candy like Skittles, Starbursts, and Jell-O, gum like Trident White peppermint gum and Mentos Freshmint Gum, cake products like Duncan Hines Creamy Vanilla Frosting, and Nabisco Chips Ahoy! cookies are just a few of the myriad food items that contain the additive.

After oral ingestion, the absorption of titanium dioxide particles is low, however they can accumulate in the body, Maged Younes, chair of the European Food Safety Authority's expert Panel on Food Additives and Flavourings, said in a May 2021 statement.